Shionogi Company Limited

Kanji Tokuyama

Mamoru Tanaka

Wataru Nagata

Teruji Tsuji

Yasuhiro Nishitani

Hiroyuki Ishitobi

Kenji Ikawa

Hiroaki Koizumi

Satoru Kawatake

Masumi Kiyokawa

A process for purifying oxacephalosporins which comprises contacting an aqueous solution of oxacephalosporin carboxylic acid (at pH lower than its pKa) with a macroporous polymeric adsorbent (specific gravity: higher than 1.05; and saturated adsorption capacity for cephalosporin C. larger than 60 mg/ml) to adsorb and thereby separate the oxacephalosporin carboxylic acid from non-adsorbable contaminants, and then eluting the adsorbed oxacephalosporin carboxylic acid with an aqueous hydrophilic organic solvent to elute and thereby separate it from non-eluting contaminants.

Purification of cephalosporins

A useful industrial chemical, oxazolinoazetidinylhydroxymethylbutenoic acid derivative (II) can be produced by oxidizing the corresponding oxazolinoazetidinylhalomethylbutenoic acid derivative(I). ##STR1## wherein R is an alkyl, aralkyl or aryl group, R.sup.1 is a hydrogen atom or a carboxy protecting group and Hal is a halogen atom.

Production of hydroxymethylbutenoic acids via oxidation

A phosphine sulfide derivative is chlorinated and hydrolyzed with little pollution problem to give the corresponding phosphine oxide derivative.

Process for preparing phosphine oxides

L-ascorbic acid is prepared from sodium 2-keto-L-gulonate by introducing gaseous hydrogen chloride in a molar ratio of about 1.5-2.0 to the sodium-2-keto-L-gulonate into a mixture composed of the sodium 2-keto-L-gulonate, ethanol and acetone at a ratio of 1:0.25-1.00:0.5-2.5 by weight at a temperature of about 25.degree.-75.degree. C. until precipitation of sodium chloride ends, removing the precipitated sodium chloride before L-ascorbic acid begins to crystalize out, maintaining the filtrate or supernatant at a temperature of about 25.degree.-75.degree. C. for a period of 5-100 hours and cooling it to yield crystals of L-ascorbic acid as a final product. A solvent inert to the L-ascorbic acid and 2-keto-L-gulonate may be added to the filtrate or supernatant with a favorable result in obtaining purer intended product.

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Osaka, Japan

Kanji Tokuyama